Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, P.R. China.
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China.
Food Funct. 2021 Oct 19;12(20):10184-10195. doi: 10.1039/d1fo02172a.
Dietary interventions, including dietary ingredients, nutrients and probiotics, exert anti-inflammatory effects in ulcerative colitis (UC). Our previous study showed that (), a promising probiotic, could protect against colitis the regulation of the immune response. However, whether it can restore aberrant tryptophan (Trp) metabolism during colitis remains unclear. In this study, untargeted serum metabolomics of patients with UC and colitis mice showed that Trp metabolism was activated, which was confirmed by quantification of Trp metabolites from a validation cohort and animal study. Integrative analysis of faecal metagenomes and serum metabolomes revealed significant associations between and three Trp metabolites. Live , pasteurised and Amuc_1100 failed to restore the reduction in Trp metabolites involved in the serotonin pathway in colitis mice. However, live , pasteurised and Amuc_1100 increased kynurenine (Kyn) but decreased 2-picolinic acid (PIC) levels and the PIC/Kyn ratio without regulating any of the genes involved in Trp metabolism, suggesting that they could suppress the Kyn pathway (KP) independent of colon tissue. In addition, they could significantly restore the enrichment of Trp metabolism mediated by faecal microbiota. Specifically, live , pasteurised and Amuc_1100 could significantly offset the reduction in indoleacetic acid (IAA) levels. Pasteurised significantly elevated the serum levels of indole acrylic acid (IA). In addition, live , pasteurised and Amuc_1100 could upregulate aryl hydrocarbon receptor (AhR) targeted genes, including , and , suggesting that could activate AhR signaling by regulating Trp metabolism, thereby attenuating colonic inflammation.
饮食干预措施，包括饮食成分、营养素和益生菌，在溃疡性结肠炎 (UC) 中发挥抗炎作用。我们之前的研究表明，（），一种有前途的益生菌，可能通过调节免疫反应来预防结肠炎。然而，它是否能在结肠炎期间恢复异常色氨酸（Trp）代谢尚不清楚。在这项研究中，对 UC 患者和结肠炎小鼠的非靶向血清代谢组学进行了研究，结果表明 Trp 代谢被激活，这通过从验证队列和动物研究中定量测定 Trp 代谢物得到了证实。粪便宏基因组和血清代谢组学的综合分析显示，与三种 Trp 代谢物之间存在显著关联。活、巴氏消毒和 Amuc_1100 未能恢复结肠炎小鼠中涉及血清素途径的 Trp 代谢物的减少。然而，活、巴氏消毒和 Amuc_1100 增加了犬尿氨酸 (Kyn) 但降低了 2-吡啶甲酸 (PIC) 水平和 PIC/Kyn 比值，而不调节 Trp 代谢途径中的任何基因，表明它们可以独立于结肠组织抑制犬尿氨酸途径 (KP)。此外，它们可以显著恢复粪便微生物群介导的 Trp 代谢的富集。具体来说，活、巴氏消毒和 Amuc_1100 可以显著抵消色氨酸代谢物水平的降低。巴氏消毒显著提高了血清吲哚丙烯酸 (IA) 水平。此外，活、巴氏消毒和 Amuc_1100 可以上调芳香烃受体 (AhR) 靶向基因，包括、和，表明可以通过调节 Trp 代谢激活 AhR 信号通路，从而减轻结肠炎症。
